Publications by authors named "Jane Gakuru"
Cerebrospinal fluid (CSF) protein levels exhibit high variability in HIV-associated cryptococcal meningitis; however, its clinical implications remain unclear. We analyzed data from 890 adults with HIV-associated cryptococcal meningitis randomized into two clinical trials in Uganda between 2015 and 2021. CSF protein was grouped into < 100 mg/dl (72%, n = 641) and ≥ 100 mg/dl (28%, n = 249).
View Article and Find Full Text PDFBackground: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.
Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023.
Article Synopsis
- - Histoplasmosis is a serious fungal infection linked to high death rates in people with advanced HIV, prompting this study to assess its global prevalence of antigenuria in HIV-positive individuals.
- - The research included 15 studies after screening nearly 1,300, revealing that 11% of individuals with HIV and 13% of those with advanced HIV had detectable Histoplasma antigens in their urine.
- - The findings suggest that those with advanced HIV, especially symptomatic patients and hospitalized individuals, could greatly benefit from routine urine antigen tests for early histoplasmosis detection.
Article Synopsis
- The IMPROVE trial aims to improve outcomes for adults suffering from HIV-associated cryptococcal meningitis by testing two TPT strategies for preventing tuberculosis (TB).
- The study will enroll 205 participants in Uganda, who will be randomized to receive either early inpatient or standard outpatient initiation of a one-month TB treatment regimen.
- The trial will assess the safety, feasibility, and treatment completion rates, with a focus on gathering data that could enhance TB prevention methods in high-risk populations.
Article Synopsis
- In a study of 890 adults with HIV-associated cryptococcal meningitis, researchers found that cerebrospinal fluid (CSF) protein levels varied significantly, impacting clinical outcomes.
- Approximately one-third of the participants had elevated CSF protein (≥100 mg/dL), leading to associations with more severe clinical presentations, such as impaired consciousness and seizures, but also indicated better fungal clearance and immune responses.
- The study concluded that higher CSF protein levels could be a useful indicator for immune activation and could help predict patient prognosis in cryptococcal meningitis.
Purpose Of Review: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Inadequate diagnostic testing and treatment regimens adapted from pulmonary tuberculosis without consideration of the unique nature of TBM are among the potential drivers. This review focuses on the progress being made in relation to both diagnosis and treatment of TBM, emphasizing promising future directions.
View Article and Find Full Text PDFCryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings.
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- Amphotericin B is the primary treatment for severe fungal infections, and a new less-toxic oral formulation called lipid nanocrystal (LNC) amphotericin has been developed for potential use.
- A clinical trial tested LNC amphotericin against traditional intravenous amphotericin for treating cryptococcal meningitis in HIV patients, focusing on safety, efficacy, and survival rates.
- Results showed that the oral formulation had comparable effectiveness and was associated with fewer severe side effects compared to intravenous treatment, suggesting it could be a safer alternative for patients.
Article Synopsis
- Health workers in Uganda are not following the Ministry of Health guidelines for screening and managing HIV-associated cryptococcal meningitis (CM), which is a concerning public health issue.
- An observational study assessed adherence at 15 different health facilities between January and June 2021, using a scoring system; the average adherence score was only 64.7%, indicating poor compliance.
- Key findings revealed that many health facilities lacked essential resources, such as potassium chloride, and failed to conduct necessary baseline tests for patients, highlighting a significant gap in care for individuals at risk of CM.
Background: Tuberculosis is a leading cause of death among women of reproductive age. However, tuberculous meningitis, the most severe form of extrapulmonary tuberculosis, is rarely discussed in pregnancy despite this being a unique period of immune modulation that may predispose women to active disease.
Methods: We identified and described cases of tuberculous meningitis among pregnant or postpartum women screened during meningitis clinical trials in Uganda from 2018 to 2022.
Diagnosis of tuberculous meningitis (TBM) remains challenging due to a paucity of high-performance diagnostics. Even those that have reasonable sensitivity are not adequate to 'rule out' TBM. Therefore, a combination of clinical factors alongside microbiological, molecular, and radiological investigations are utilized, depending on availability.
View Article and Find Full Text PDFBackground: Cryptococcal meningitis is a leading cause of mortality in advanced HIV disease. A positive cerebrospinal fluid cryptococcal antigen (CrAg) test defines cryptococcal meningitis. Herein, we present a patient with serum and cerebrospinal fluid CrAg negative cryptococcal meningitis, despite a positive cerebrospinal fluid India ink examination and quantitative culture.
View Article and Find Full Text PDFAntiretroviral therapy (ART), while essential in combatting tuberculosis (TB) and HIV coinfection, is often complicated by the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Depending on the TB disease site and treatment status at ART initiation, this immune-mediated worsening of TB pathology can take the form of paradoxical TB-IRIS, unmasking TB-IRIS, or CNS TB-IRIS. Each form of TB-IRIS has unique implications for diagnosis and treatment.
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